High-volume prostate biopsy core involvement is not associated with an increased risk of cancer recurrence following 5-fraction stereotactic body radiation therapy monotherapy.

PURPOSE: Percentage of positive cores involved on a systemic prostate biopsy has been established as a risk factor for adverse oncologic outcomes and is a National Comprehensive Cancer Network (NCCN) independent parameter for unfavorable intermediate-risk disease. Most data from a radiation standpoint was published in an era of conventional fractionation. We explore whether the higher biological dose delivered with SBRT can mitigate this risk factor. METHODS: A large single institutional database was interrogated to identify all patients diagnosed with localized prostate cancer (PCa) treated with 5-fraction SBRT without ADT. Pathology results were reviewed to determine detailed core involvement as well as Gleason score (GS). High-volume biopsy core involvement was defined as ≥ 50%. Weighted Gleason core involvement was reviewed, giving higher weight to higher-grade cancer. The PSA kinetics and oncologic outcomes were analyzed for association with core involvement. RESULTS: From 2009 to 2018, 1590 patients were identified who underwent SBRT for localized PCa. High-volume core involvement was a relatively rare event observed in 19% of our cohort, which was observed more in patients with small prostates (p < 0.0001) and/or intermediate-risk disease (p = 0.005). Higher PSA nadir was observed in those patients with low-volume core involvement within the intermediate-risk cohort (p = 0.004), which was confirmed when core involvement was analyzed as a continuous variable weighted by Gleason score (p = 0.049). High-volume core involvement was not associated with biochemical progression (p = 0.234). CONCLUSIONS: With a median follow-up of over 4 years, biochemical progression was not associated with pretreatment high-volume core involvement for patients treated with 5-fraction SBRT alone. In the era of prostate SBRT and MRI-directed prostate biopsies, the use of high-volume core involvement as an independent predictor of unfavorable intermediate risk disease should be revisited.

Exploring Variation in the Use of Conservative Management for Low-risk Prostate Cancer in the Veterans Affairs Healthcare System.

Current guidelines recommend conservative management as the preferred option for most low-risk prostate cancer cases, with certain possible exceptions (age <55yr, African Americans, and high-volume grade group 1). Although previous studies have documented substantial heterogeneity in the uptake of conservative management, less is known about the underlying reason for this variation and whether it is due to guideline-concordant factors (age, race, and biopsy cancer volume). We explored variation in the use of conservative management for low-risk prostate cancer among 20 597 men diagnosed in the US Veterans Affairs health care system from 2010 to 2016. Conservative management increased substantially over this time from 51% to 76% (p< 0.001). However, there was substantial variation by facility (35-100%). Multivariable analysis revealed that patient factors included in the guidelines (e.g., age and biopsy cores), other patient factors (eg, marital status and PSA) and non-patient factors (eg, geographic region, case volume, year) were associated with conservative management use. In conclusion, even within an integrated health care system, there remains significant heterogeneity in the uptake of conservative management for low-risk prostate cancer. Both guideline-concordant factors and other factors not discussed in the guidelines were associated with conservative management use. PATIENT SUMMARY: In the US Veterans Affairs health care system the vast majority of men with low-risk prostate cancer were managed conservatively by 2016, although there was significant variation by facility. Patient factors specifically mentioned in guidelines had the greatest impact on prediction of conservative management.

Informational needs during active surveillance for prostate cancer: A qualitative study.

OBJECTIVE: To understand the informational needs during active surveillance (AS) for prostate cancer from the perspectives of patients and providers. METHODS: We conducted seven focus groups with 37 AS patients in two urban clinical settings, and 24 semi-structured interviews with a national sample of providers. Transcripts were analyzed using applied thematic analysis, and themes were organized using descriptive matrix analyses. RESULTS: We identified six themes related to informational needs during AS: 1) more information on prostate cancer (biopsy features, prognosis), 2) more information on active surveillance (difference from watchful waiting, testing protocol), 3) more information on alternative management options (complementary medicine, lifestyle modification), 4) greater variety of resources (multiple formats, targeting different audiences), 5) more social support and interaction, and 6) verified integrity of information (trusted, multidisciplinary and secure). CONCLUSIONS: Patients and providers described numerous drawbacks to existing prostate cancer resources and a variety of unmet needs including information on prognosis, AS testing protocols, and lifestyle modification. They also expressed a need for different types of resources, including interaction and unbiased information. PRACTICAL IMPLICATIONS: These results are useful to inform the design of future resources for men undergoing AS.

New and Established Technology in Focal Ablation of the Prostate: A Systematic Review.

CONTEXT: Focal therapy of prostate cancer has been proposed as an alternative to whole-gland treatments. OBJECTIVE: To summarize the evidence regarding sources of energy employed in focal therapy. EVIDENCE ACQUISITION: Embase and Medline (PubMed) were searched from 1996 to October 31, 2015 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Ongoing trials were selected from electronic registries. The stage of assessment of each source of energy was determined using the Idea, Development, Exploration, Assessment, Long-term study recommendations. EVIDENCE SYNTHESIS: Thirty-seven articles reporting on 3230 patients undergoing focal therapy were selected. Thirteen reported on high-intensity focused ultrasound, 11 on cryotherapy, three on photodynamic therapy, four on laser interstitial thermotherapy, two on brachytherapy, three on irreversible electroporation, and one on radiofrequency. High-intensity focused ultrasound, cryotherapy, photodynamic therapy, and brachytherapy have been assessed in up to Stage 2b studies. Laser interstitial thermotherapy and irreversible electroporation have been evaluated in up to Stage 2a studies. Radiofrequency has been evaluated in one Stage 1 study. Median follow-up varied between 4 mo and 61 mo, and the median rate of serious adverse events ranged between 0% and 10.6%. Pad-free leak-free continence and potency were obtained in 83.3-100% and 81.5-100%, respectively. In series with intention to treat, the median rate of significant and insignificant disease at control biopsy varied between 0% and 13.4% and 5.1% and 45.9%, respectively. The main limitations were the length of follow-up, the absence of a comparator arm, and study heterogeneity. CONCLUSIONS: Focal therapy has been evaluated using seven sources of energy in single-arm retrospective and prospective development studies up to Stage 2b. Focal therapy seems to have a minor impact on quality of life and genito-urinary function. Oncological effectiveness is yet to be defined against standard of care. PATIENT SUMMARY: Seven sources of energy have been employed to selectively ablate discrete areas of prostate cancer. There is high evidence that focal therapy is safe and has low detrimental impact on continence and potency. The oncological outcome has yet to be evaluated against standard of care.

Effect of soy protein isolate supplementation on biochemical recurrence of prostate cancer after radical prostatectomy: a randomized trial.

IMPORTANCE: Soy consumption has been suggested to reduce risk or recurrence of prostate cancer, but this has not been tested in a randomized trial with prostate cancer as the end point. OBJECTIVE: To determine whether daily consumption of a soy protein isolate supplement for 2 years reduces the rate of biochemical recurrence of prostate cancer after radical prostatectomy or delays such recurrence. DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind trial conducted from July 1997 to May 2010 at 7 US centers comparing daily consumption of a soy protein supplement vs placebo in 177 men at high risk of recurrence after radical prostatectomy for prostate cancer. Supplement intervention was started within 4 months after surgery and continued for up to 2 years, with prostate-specific antigen (PSA) measurements made at 2-month intervals in the first year and every 3 months thereafter. INTERVENTION: Participants were randomized to receive a daily serving of a beverage powder containing 20 g of protein in the form of either soy protein isolate (n=87) or, as placebo, calcium caseinate (n=90). MAIN OUTCOMES AND MEASURES: Biochemical recurrence rate of prostate cancer (defined as development of a PSA level of ≥0.07 ng/mL) over the first 2 years following randomization and time to recurrence. RESULTS: The trial was stopped early for lack of treatment effects at a planned interim analysis with 81 evaluable participants in the intervention group and 78 in the placebo group. Overall, 28.3% of participants developed biochemical recurrence within 2 years of entering the trial (close to the a priori predicted recurrence rate of 30%). Among these, 22 (27.2%) occurred in the intervention group and 23 (29.5%) in the placebo group. The resulting hazard ratio for active treatment was 0.96 (95% CI, 0.53-1.72; log-rank P = .89). Adherence was greater than 90% and there were no apparent adverse events related to supplementation. CONCLUSION AND RELEVANCE: Daily consumption of a beverage powder supplement containing soy protein isolate for 2 years following radical prostatectomy did not reduce biochemical recurrence of prostate cancer in men at high risk of PSA failure. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00765479.

LHRH Agonists for the Treatment of Prostate Cancer: 2012.

The most recent guidelines on prostate cancer screening from the American Urological Association (2009), the National Comprehensive Cancer Network (2011), and the European Association of Urology (2011), as well as treatment and advances in disease monitoring, have increased the androgen deprivation therapy (ADT) population and the duration of ADT usage as the first-line treatment for metastatic prostate cancer. According to the European Association of Urology, gonadotropin-releasing hormone (GnRH) agonists have become the leading therapeutic option for ADT because they avoid the physical and psychological discomforts associated with orchiectomy. However, GnRH agonists display several shortcomings, including testosterone (T) surge ("clinical flare") and microsurges. T surge delays the intended serologic endpoint of T suppression and may exacerbate clinical symptoms. Furthermore, ADT manifests an adverse-event spectrum that can impact quality of life with its attendant well-documented morbidities. Strategies to improve ADT tolerability include a holistic management approach, improved diet and exercise, and more specific monitoring to detect and prevent T depletion toxicities. Intermittent ADT, which allows hormonal recovery between treatment periods, has become increasingly utilized as a methodology for improving quality of life while not diminishing chronic ADT efficacy, and may also provide healthcare cost savings. This review assesses the present and potential future role of GnRH agonists in prostate cancer and explores strategies to minimize the adverse-event profile for patients receiving ADT.

Silodosin for the treatment of benign prostatic hyperplasia: pharmacology and cardiovascular tolerability.

Relief of benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms by α-blockers (α1-adrenoceptor antagonists) is mediated primarily through the blockade of α(1A)-receptors, leading to relaxation of smooth muscle in the prostate and bladder neck. Early α-blockers that were nonselective for adrenoceptor subtypes have been associated with blood pressure-related adverse effects, such as orthostatic hypotension, that may be attributed at least in part to the blockade of α(1B)-adrenoceptors in arterial vessels. Silodosin, a novel α-blocker with exceptionally high selectivity for α(1A-) versus α(1B)-adrenoceptors, was recently approved in the United States for the treatment of urinary symptoms related to BPH. The unique receptor selectivity profile likely accounts for some of the desirable clinical features of the drug. Silodosin possesses an excellent cardiac- and blood pressure-related safety profile, and data have demonstrated that it does not promote QT-interval prolongation. Therapeutic doses of silodosin are safe for men with mild-to-moderate liver dysfunction; dosage adjustment is recommended in those with moderate renal impairment. The drug should not be taken with potent cytochrome P450 3A4 inhibitors. Silodosin may be especially beneficial in patients who need to maximize cardiovascular tolerability.

Durability and retreatment rates of minimal invasive treatments of benign prostatic hyperplasia: a cross-analysis of the literature.

BACKGROUND: Transurethral resection of the prostate (TURP) has been the gold standard of the treatment of benign prostatic hyperplasia (BPH). In recent years there has been a significant shift in the treatment of BPH and guidelines emphasize minimally invasive surgery as a new treatment option. Minimal invasive technologies (MITs), such as transurethral microwave thermotherapy (TUMT), laser ablations, transurethral needle ablation (TUNA) have emerged as an alternative to the TURP. OBJECTIVES: To assess the retreatment rates of the most commonly used minimal invasive techniques. SEARCH STRATEGY: Durability articles were selected by using defined search terms using PubMed as search engine. RESULTS: Comparing to the overall retreatment rates of MITs the results show that TUMT, holmium laser enucleation of the prostate (HoLEP) and contact laser vaporization (CLV) are among the treatments with the lowest retreatment rates. Studies show no significant differences in retreatment rates between TUMT and TURP. CONCLUSION: A review of the current literature, long term results and retreatment rates of MITs shows large variability in outcomes and retreatment rates. The true definition of a MIT remains unclear. High energy TUMT deserves reconsideration in clinical practices, due to low retreatment rates and the low need of anesthetics.

The effect of local compression and topical epinephrine on perioperative bleeding and degree of urinary extravasation on postoperative cystogram following radical retropubic prostatectomy.

OBJECTIVE: To evaluate the efficacy of local compression and topical epinephrine in controlling perioperative bleeding during open radical retropubic prostatectomy (ORRP) and its impact on the degree of urinary extravasation on initial postoperative cystogram. METHODS: Between September 2005 to March 2009, 476 men underwent ORRP performed by a single surgeon. Group 1 (n = 200) underwent ORRP between September 2005 and November 2006 without pelvic compression; Group 2 (n = 76) underwent ORRP between November 2006 and May 2007 and a dry laparotomy pad was positioned in the pelvis immediately prior to abdominal wound closure; Group 3 (n = 200) underwent ORRP between May 2007 and March 2009 with a epinephrine soaked laparotomy pad positioned in the pelvis prior to abdominal wound closure. Hematocrit values were obtained prior to anesthesia induction, upon arrival in the recovery room and at hospital discharge in order to estimate intraoperative and postoperative bleeding. The number of allogenic and autologous units transfused was recorded. The utility of compressing the pelvis with a pad was examined by comparing estimated postoperative bleeding between Group 1 versus Groups 2 and 3 and the hemostatic utility of soaking the pad in epinephrine was examined by comparing Group 2 versus 3. Systolic and diastolic blood pressure and pulse measurements were obtained at baseline and 5 and 10 minutes after introducing the epinephrine pad. The relationship between estimated blood loss and degree of extravasation on initial postoperative cystogram was investigated. RESULTS: Estimated intraoperative, postoperative and total blood loss (mean change in Hct) was 12.2, 2.3, 14.2, in Group 1, 10.0, 1.5, 11.1 in Group 2, and 10.8, 2.1, and 12.6 in Group 3. Estimated intraoperative and total blood loss was significantly less in the men treated with a compression pad (Groups 2 and 3) versus no pad (Group 1). There were no significant differences in number of patients transfused, the number of units transfused or the degree of extravasation on postoperative cystograms between Group 1 versus Group 2 and 3 or Group 2 versus 3. However, postoperative bleeding was significantly less in Group 2 compared to Group 3. Mean systolic and diastolic blood pressure and pulse values were unchanged from baseline after epinephrine use. CONCLUSIONS: Local compression of the pelvis with or without epinephrine prior to abdominal wound closure does not appear to have beneficial effects on reducing postoperative bleeding and decreasing the degree of urinary extravasation on cystogram following ORRP. While the use of topical epinephrine appears to be safe and relatively inexpensive, at the concentrations used in our study it does not appear to facilitate postoperative hemostasis.